Gene Editing Trials: Navigating the Clinical Frontier

Abstract

Gene editing, led by CRISPR technologies, has transitioned from experimental research to clinical reality, marked by milestones such as FDA approval of exagamglogene autotemcel (exa-cel) for hemoglobinopathies and bespoke in vivo interventions in ultra-rare diseases. This editorial examines both somatic and germline gene editing trials, using the recent personalized CRISPR application for CPS1 deficiency as an illustrative case within the broader landscape. We analyze operational complexities—adaptive trial designs, manufacturing logistics, and long-term patient follow-up—and evolving regulatory frameworks, including IRB/IBC review and FDA guidance on genome editing products. Commercial considerations for sponsors and CROs are discussed, focusing on pricing models for one-time curative therapies, intellectual property dynamics, and strategic collaborations. We highlight site readiness imperatives, from GMP infrastructure to specialized training and “Gene Therapy Ready” networks, and ethical imperatives around germline editing. Industry professionals across sponsors, CROs, IRBs, vendors, and research sites must collaboratively evolve to steward gene editing innovations responsibly, balancing rapid access with safety, transparency, and equitable patient care.